Effects of Frontopolar TMS in Alcohol Craving

NCT ID: NCT07064590

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-16

Study Completion Date

2027-05-31

Brief Summary

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The goal of this interventional study is to learn if continuous theta burst stimulation (cTBS) applied over the left frontopolar cortex can reduce psychological, physiological, and neurobiological markers of alcohol craving in patients with alcohol dependence (AD).

The main questions it aims to answer are:

* Does cTBS over the left frontopolar cortex reduce psychological and physiological measures of alcohol craving in individuals with AD?
* Are baseline structural and functional brain connectivity patterns associated with individual differences in cTBS-induced changes in craving?

The participants will:

* Receive cTBS over the left frontopolar cortex using an accelerated protocol comprising 15 TMS-sessions on five consecutive days
* Undergo psychological and physiological assessments of alcohol craving before and after the TMS intervention
* Complete magnetic resonance imaging (MRI) sessions to assess baseline brain structural and functional connectivity

This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions.

Detailed Description

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Alcohol dependence (AD) is a prevalent and debilitating condition characterized by a chronic inability to control alcohol consumption despite adverse consequences. Current treatment options have limited efficacy, highlighting the pressing need for innovative approaches. Continuous Theta Burst Stimulation (cTBS) is a form of transcranial magnetic stimulation (TMS) that has shown promise in modulating brain activity associated with craving and addiction.

This study aims to explore the effects of cTBS applied over the left frontopolar cortex on psychological, physiological, and neurobiological markers of alcohol craving in patients with AD. Specifically, this study will assess TMS-induced changes in psychological alcohol craving using the Penn Alcohol Craving Scale (PACS), and physiological alcohol craving using physiological craving markers, including heart rate (HR), skin temperature (ST) and skin conductance (SC), and their changes during Virtual Reality Cue Exposure and Craving Assessment (VR-CECA) before and after the TMS intervention. Additionally, the study aims to explore the relationship between neurobiological craving markers utilizing baseline structural and functional brain connectivity as assessed by magnetic resonance imaging (MRI) and TMS-induced changes in psychological and physiological alcohol craving.

This study aims to include a total of 34 patients aged 18-65 years with an ICD-10 diagnosis of AD. All participants undergo 15 sessions of accelerated cTBS targeting the left frontopolar cortex over five consecutive days using neuronavigation based on individual MRI scans. Clinical (questionnaires, diagnostic interviews) and behavioural (VR-CECA) assessments are conducted at two time points: pre-TMS intervention and post-TMS intervention. Structural and functional MRI scans are acquired before the TMS intervention to assess individual brain connectivity.

The primary outcome will be the TMS-induced change in psychological alcohol craving assessed with the PACS. Secondary outcomes include TMS-induced changes in physiological craving markers (HR, ST, and SC) during VR-CECA and TMS-induced changes and psychopathological states that will be assessed through a battery of clinical questionnaires.

This study hypothesizes that frontopolar cTBS will reduce psychological and physiological alcohol craving in patients with AD. Additionally, this study expects that baseline structural and functional connectivity will predict TMS-induced changes in physiological alcohol craving, providing insights into individual brain network variability on the effect of frontopolar cTBS.

This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions. If successful, this could lead to more targeted and effective interventions for AD, ultimately improving patient outcomes.

Conditions

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Alcohol Addiction

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Frontopolar cTBS Intervention

Participants in this arm will receive 15 sessions of continuous theta burst stimulation (cTBS) over the left frontopolar cortex across 5 consecutive days (3 sessions/day) using neuronavigation based on individual MRI. The stimulation intensity is set at 110% of the resting motor threshold. Virtual Reality Cue Exposure and Craving Assessment (VR-CECA) and psychological craving assessment will be performed before and after the TMS intervention. Baseline structural and functional MRI scans will be acquired before stimulation for brain connectivity analysis.

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS)

Intervention Type DEVICE

Patients will receive cTBS, a five-minute protocol with inhibitory effects over the left frontal pole, using an accelerated design comprising three sessions daily for five consecutive days (15 sessions total). Stimulation will be delivered using a Magventure TMS device routinely used in clinical practice at the Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Frankfurt. TMS is generally well tolerated, with mild headache or scalp discomfort as common side effects. Localization will be based on individual MRI data: after cortical parcellation with FreeSurfer 7.4.1, the left frontal pole centroid will be extracted. Coil placement will be neuronavigated using the Localite Neuronavigator. Stimulation will be applied at 110% resting motor threshold (rMT; 3-pulse bursts at 50 Hz, 5 Hz interburst; 1800 pulses/train; 60 s intertrain). Intensity may be gradually increased until 110% rMT is reached.

Interventions

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Transcranial Magnetic Stimulation (TMS)

Patients will receive cTBS, a five-minute protocol with inhibitory effects over the left frontal pole, using an accelerated design comprising three sessions daily for five consecutive days (15 sessions total). Stimulation will be delivered using a Magventure TMS device routinely used in clinical practice at the Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Frankfurt. TMS is generally well tolerated, with mild headache or scalp discomfort as common side effects. Localization will be based on individual MRI data: after cortical parcellation with FreeSurfer 7.4.1, the left frontal pole centroid will be extracted. Coil placement will be neuronavigated using the Localite Neuronavigator. Stimulation will be applied at 110% resting motor threshold (rMT; 3-pulse bursts at 50 Hz, 5 Hz interburst; 1800 pulses/train; 60 s intertrain). Intensity may be gradually increased until 110% rMT is reached.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* adults aged 18-65
* ICD-10 diagnosis of alcohol dependence
* Ability to give consent
* Sinus rhythm in ECG

Exclusion Criteria

* Current psychotic symptoms in patients with psychotic disorders (F20, F23, F10.5)
* Contraindication against TMS or MRI
* Severe neurological disorders such as epilepsy, stroke, neuroinflammatory disorders (e.g., multiple sclerosis). A history of seizures only in the context of alcohol withdrawal does not represent a contraindication, unless the seizure happened in the last 3 weeks before study inclusion.
* Acute withdrawal symptoms (CIWA-Ar \> 5)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Goethe University

OTHER

Sponsor Role lead

Responsible Party

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Jonathan Repple

Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jonathan Repple, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

Mathias Luderer, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

Maren Schmidt-Kassow, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

Locations

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Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität

Frankfurt am Main, Hesse, Germany

Site Status RECRUITING

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität

Frankfurt am Main, Hesse, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Franka Timm, M.Sc.

Role: CONTACT

+49 171 9225424

Jonathan Repple, Prof. Dr.

Role: CONTACT

+49 17641633481

Facility Contacts

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Franka Timm

Role: primary

+491719225424

Jonathan Repple, Prof. Dr.

Role: backup

+49 17641633481

References

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Williams JB, Kobak KA. Development and reliability of a structured interview guide for the Montgomery Asberg Depression Rating Scale (SIGMA). Br J Psychiatry. 2008 Jan;192(1):52-8. doi: 10.1192/bjp.bp.106.032532.

Reference Type BACKGROUND
PMID: 18174510 (View on PubMed)

Nakovics H, Diehl A, Geiselhart H, Mann K. [Development and validation of an overall instrument to measure craving across multiple substances: the Mannheimer Craving Scale (MaCS)]. Psychiatr Prax. 2009 Mar;36(2):72-8. doi: 10.1055/s-2008-1067546. Epub 2008 Oct 15. German.

Reference Type BACKGROUND
PMID: 18924060 (View on PubMed)

Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.

Reference Type BACKGROUND
PMID: 10470970 (View on PubMed)

Vollstadt-Klein S, Lemenager T, Jorde A, Kiefer F, Nakovics H. Development and validation of the craving automated scale for alcohol. Alcohol Clin Exp Res. 2015 Feb;39(2):333-42. doi: 10.1111/acer.12636.

Reference Type BACKGROUND
PMID: 25684052 (View on PubMed)

Other Identifiers

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2024-2021

Identifier Type: -

Identifier Source: org_study_id

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